The Molecular and Genetic Toxicology Research Core is directed by Dr. Toby Rossman, and consists of ten NIEHS Center investigators. A primary goal of this Core is to elucidate the effects of environmental agents on the structure and function of cellular genes and macromolecules, including those involved with transcription control and to identify proteins conferring resistance to environmental agents. Most of the studies in this Core are carried out in-vitro systems. The Molecular and Genetic Toxicology Research Core uses the tools of chemistry and molecular biology (and increasingly those of mathematics) to elucidate the toxicological effects of chemicals. While this Core is particularly strong, in studies on inorganic compounds, such as arsenic, nickel, chromium and cadmium; the Core is not limited to these compounds. The molecular toxicological effects of metals and other agents are studied by examining their interactions with DNA and with proteins that have structural, regulatory or enzymatic activities (such as receptors, efflux pumps, signaling, leading to transcriptional changes and DNA polymerases). The biochemistry of metal-mediated active oxygen species and the biological effects that result from such reactive radicals is of interest to this Core. Another focus is on mutational specificity of carcinogens and site-specific mutagenesis of particular DNA lesions. Other areas of interest include the molecular basis for resistance to environmental agents and the effects of estrogen-like compounds on gene expression. The proposed studies within this research core are focused mainly on expanding ongoing studies using cellular and molecular techniques. These studies can be divided into three groups: 1) DNA damage, repair and mutagenesis, 2) gene regulation and 3) receptors and signal transduction.